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Researchers reverse juvenile diabetes in animal model

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center researchers Massimo Trucco, MD, and Nick Giannoukakis, PhD, observed marked amelioration of diabetes in a mouse model by a novel treatment strategy involving specific modification of the animal's own dendritic cells, thereby reversing diabetes in animal studies.

The U.S. Food and Drug Administration (FDA) approved the start of a clinical trial to evaluate the safety and feasibility of the treatment (Phase 1 trial). The trial is expected to begin sometime this spring and will include at least 15 patients over the age of 18, with type 1 diabetes.

Dr. Trucco, director of the Division of Immunogenetics at Children's, and his research team will collaborate with Theresa Whiteside, PhD, scientific director at the University of Pittsburgh Cancer Institute.

Dr. Trucco and his team found that by removing dendritic cells from the blood during a two- to four-hour procedure, some 20 million dendritic cells can be harvested.

Dendritic cells are cells found in the bloodstream and normally function as one of nature's most efficient immune function cells. The cells identify foreign substances such as cancer cells, process these foreign substances, and then jumpstart the immune response by bringing these foreign substances to the attention of T cells.

Once harvested, researchers then combine the dendritic cells with specific blockers of molecules, known as CD40, CD80 and CD86, all of which can be synthesized in a laboratory. This treatment strategy was found to inhibit the interaction and destructive effect of T cells on the insulin-producing beta cells of the pancreas, a process that is known to be a critical part of how diabetes occurs.

Subcutaneous injection of dendritic cells into the abdominal/pelvic area near the pancreas and lymph nodes, blocks the T cells as they travel to the pancreas to destroy beta cells.

"We did this in mice, giving them si x injections over the course of several weeks. The injections interrupted the T cell and beta cell interaction, allowing the beta cells in the pancreas to regenerate. This enabled the pancreas of the mice to begin producing insulin again," said Dr. Trucco, who also is the Hillman Professor of Pediatric Immunology at Children's Hospital and a professor of Pediatrics at the University of Pittsburgh School of Medicine. "The injections proved capable of stopping this vicious cycle, and through this process curing type 1 diabetes in a mouse."

Until now, scientists weren't sure why the immune system attacks the beta cells, but the result is that the body stops producing insulin. When that happens, glucose builds up in the blood, but the body's cells starve to death.

"We are very excited to begin the clinical trials and see if this process will work in patients with type 1 diabetes," said Dr. Trucco. "A type 1 diabetes diagnosis can be devastating for children and their families. We hope this trial will have results that are life-altering for patients who suffer from this disease."

In addition, Dr. Trucco and his team want to combine the dendritic cells with small portions (i.e. peptides) of insulin. Dr. Trucco believes that adding small doses of insulin to the dendritic cells will help guide the dendritic cells directly to the T cells. Adding the insulin ensures the dendritic cells are used specifically to block the T cell destruction of the beta cells, and not otherwise interrupt a person's immunity. In other words, the dendritic cells are led directly to the target, the T cells that are causing the malfunction of the pancreas, and not to another part of the body.

Type 1 diabetes also is known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. While type 2 diabetes typically strikes adults, the National Institutes of Health (NIH) reports that more than 1 million children and teenagers (age 19 and younger) have type 1 diabetes. According to the NIH, 5 percent to 10 percent of diagnosed diabetes cases in the United States are type 1 diabetes.

Type 1 diabetes is regarded as an autoimmune disease because a person's immune system attacks and destroys the beta cells in the pancreas that produce insulin. Symptoms of type 1 diabetes usually develop over a short period of time and include increased thirst, frequent urination, constant hunger, weight loss, blurred vision and extreme fatigue. People with type 1 diabetes require numerous daily injections of insulin to survive.

About Dr. Trucco

Massimo Trucco, MD, has dedicated his life's work to finding a cure for diabetes -- finding a cure is a personal quest for him. As an international leader in the field of immunogenetics, Dr. Trucco has pioneered numerous important studies and also maintains a federally funded national bone marrow HLA typing center within his lab.With this funding, Dr. Trucco and his team are able to continue their landmark research into improving the prediction of type 1 diabetes and understanding and managing its complications. Building on his discovery in 1994 that type 1 diabetes susceptibility may be genetic in nature and triggered by viruses, Dr. Trucco's discoveries have continue to lead to better processes for molecular typing for matching bone marrow donors and recipients, the ability to identify those at risk for diabetes, an understanding of the link between a common virus and type 1 diabetes, and a potential cure for the pancreatic damage that causes insulin dependence.

Diabetes and children statistics:

  • The risk of developing type 1 diabetes is higher than virtually all other severe chronic diseases of childhood.
  • Peak incidence occurs during puberty, around 10 to 12 years of age in girls, and around 12 to 14 years of age in boys.
  • The symptoms of type 1 diabetes can resemble the flu in children.
  • Type 1 diabetes tends to run in families. Brothers and sisters of children with type 1 diabetes have about a 10 percent chance of developing the disease by age 50.
  • The identical twin of a person with type 1 diabetes has a 25 percent to 50 percent chance of developing type 1 diabetes.


Source:Children's Hospital of Pittsburgh

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